In this competing renewal application for a K02 award, Dr. Andrew Leuchter proposes a line of research and career enhancement aimed at improving outcomes of treatment for depression. Between 25 - 40 percent of patients with depression fail to respond to the first antidepressant prescribed, and these patients may suffer a protracted course of depression. Preliminary studies indicate that brain function measured with quantitative electroencephalographic (QEEG) cordance may be used prior to treatment, to predict which antidepressant medication is most likely to benefit an individual patient, as well as after treatment has started, to detect antidepressant effectiveness before symptoms improve. This application has three specific aims: 1) to verify the discriminative power of cordance in predicting and detecting treatment response for two antidepressants with different mechanisms of action; 2) to establish the relationship of cordance measurements to other putative predictors of antidepressant response, including cerebral metabolism and structure as well as clinical factors (age and symptom type); and, 3) in a developmental aim, to enhance Dr. Leuchter's skill in the areas of measuring treatment outcome and assessing the impact of predictors on treatment effectiveness. For his primary research study, Dr. Leuchter proposes a plan which will enroll 96 younger and older adult subjects in a double-masked protocol. Subjects will be treated with either fluoxetine 20/40 mg. or venlafaxine 150/225 mg., to determine whether cordance measurements are reliably associated with differential short-term response to antidepressant medications. Putative predictors of response such as pre- and post-treatment FDG-PET, volumetric MRI measurements, and clinical symptoms will be examined to identify the physiologic processes and structural features which contribute to the association between cordance and short-term treatment outcome. This study is part of an overall plan to enhance Dr. Leuchter's research activities and skills in interventions outcomes research. He will work with two consultants, Drs. Kenneth Wells and Lynn Fairbanks, to implement new methods and enhance his skills in intervention outcomes research. He will expand his research to include new methods to examine patterns of response, and will utilize additional functional outcome measures. In a developmental phase of this study, he also will initiate projects to examine the effectiveness of cordance and other putative predictors in improving long-term treatment outcomes. These effectiveness projects will include introduction of predictors into the usual treatment setting, and examination of cost-effectiveness and long-term treatment outcomes.